Dataset Information

Prefrontal cortex cytoplasmic proteome and machine learning-based predictors of resilience towards chronic social isolation in rats

ABSTRACT: Chronic social isolation (CSIS) generates two stress-related phenotypes, resilience and susceptibility. Although brain energy metabolism is important in regulating social behaviors, the molecular mechanisms underlying CSIS resilience remain unclear. To identify protein changes and altered biochemical pathways and processes for resilience to CSIS, prefrontal cortical cytosolic proteomic profiling was performed comparing CSIS-resilient with CSIS-susceptible and control rats. Potential predictive proteins discriminating between the CSIS-resilient and CSIS-susceptible groups were identified by support vector machine-based sequential feature selection and random forest-based feature importance scores. Predominantly decreased levels of glycolytic enzymes, G protein-coupled receptor proteins, Ras subfamily of GTPase proteins, and antioxidant proteins were found in CSIS-resilient vs. CSIS-susceptible groups. Altered levels of Gapdh and proteins involved in microtubule and cytoskeletal organization, and calcium-binding proteins were identified between the two phenotypes. These dynamic changes were accompanied by increased levels of proteins involved in GABA synthesis, the proteasome system, nitrogen metabolism, and chaperone-mediated protein folding. The overall ratio of significantly up- and down-regulated cytosolic proteins suggests adaptive cellular alterations as part of the stress-coping process specific for the CSIS-resilient phenotype.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Dragana Filipovic

LAB HEAD: Dragana Filipović

PROVIDER: PXD048641 | Pride | 2024-04-23

REPOSITORIES: Pride

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Publications

Prefrontal Cortex Cytosolic Proteome and Machine Learning-Based Predictors of Resilience toward Chronic Social Isolation in Rats.

Filipović Dragana D Novak Božidar B Xiao Jinqiu J Tadić Predrag P Turck Christoph W CW

International journal of molecular sciences 20240306 5

Chronic social isolation (CSIS) generates two stress-related phenotypes: resilience and susceptibility. However, the molecular mechanisms underlying CSIS resilience remain unclear. We identified altered proteome components and biochemical pathways and processes in the prefrontal cortex cytosolic fraction in CSIS-resilient rats compared to CSIS-susceptible and control rats using liquid chromatography coupled with tandem mass spectrometry followed by label-free quantification and STRING bioinforma ...[more]

PMID: 38474271

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Project description:Background: Examining transcriptional regulation by existing antidepressants in key neural circuits implicated in depression, and understanding the relationship to transcriptional mechanisms of susceptibility and natural resilience, may help in the search for new therapeutics. Further, given the heterogeneity of treatment response in human populations, examining both treatment response and non-response is critical. Methods: We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine (14 daily injections), and a rapidly acting, experimental, non-monoamine-based antidepressant, ketamine (single injection), in mice subjected to chronic social defeat stress, a validated model of depression, and used RNA-sequencing to analyze transcriptional profiles associated with susceptibility, resilience and antidepressant response and non-response in prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. Results: We identified approximately equal numbers of responder and non-responder mice following ketamine or imipramine treatment. Ketamine induced more expression changes in hippocampus than other brain regions; imipramine induced more expression changes in nucleus accumbens and amygdala. Transcriptional profiles in ketamine and imipramine responders were most similar in PFC, where the least transcriptional regulation occurred for each drug. Non-response reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptible associated transcriptional changes as well as induced resilient associated transcription in PFC, with effects varying by drug and brain region studied. Conclusions: We generated a uniquely large resource of gene expression data in four inter-connected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by both antidepressant drugs and in both reversing susceptibility and inducing resilience associated molecular adaptations. In addition, we found region-specific effects of each drug suggesting both common and unique effects of imipramine versus ketamine. mRNA profiles of susceptibility to chronic social defeat stress as well as treatment response were generated across 4 separate brain regions, with a sample size of 3-5 per group.

Dataset Information

Prefrontal cortex cytoplasmic proteome and machine learning-based predictors of resilience towards chronic social isolation in rats

Publications

Prefrontal Cortex Cytosolic Proteome and Machine Learning-Based Predictors of Resilience toward Chronic Social Isolation in Rats.

Similar Datasets

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